Pain is an unpleasant sensory or emotional experience that is associated with actual or potential tissue damaging stimuli. It is always an individual and subjective sensation, which may be acute (nociceptive), elicited by noxious stimuli, or chronic pain that has outlived its usefulness to preserve tissue integrity. The perception of pain takes mainly place at the cortex, and it may be suppressed in deep sedation and anesthesia by the general (global) inhibitory effects of sedative drugs and anesthetic agents. The responses to noxious stimulus may also be suppressed when the pain signal pathway is sufficiently suppressed at the subcortical level, often in the region of the brainstem and spinal cord. Both cortical and subcortical mechanisms play a role in pain management in modern surgical anesthesia or intensive care.
Stress is defined as a non-specific response of the body to any demand made upon it which results in symptoms such as rise in the blood pressure, release of hormones, quickness of breathe, tightening of muscles, perspiration, and increased cardiac activity. Stress is not necessarily negative. Some stress keeps us motivated and alert, while too little stress may create problems. However, too much stress can trigger problems with mental and physical health, particularly over a prolonged period of time.
The present invention relates to the determination of clinical stress, which here refers to stress induced by an underlying disease or treatment.
Sedation is a drug-induced state of a patient, during which the patient may respond normally to verbal commands or tactile stimulation and is not agitated or anxious (mild sedation), or during which the patient responds only to loud commands or tactile stimulation (moderate or conscious sedation), or during which the patient is unconscious and not easily arousable, but responds only to repeated or painful stimulation (deep or unconscious sedation). Anesthesia, in turn, is the deepest drug-induced state of sedation, during which the patient is not arousable, even by painful stimulation.
Agitation is often defined as the motor restlessness that accompanies anxiety. Mild or moderate sedation is induced to remove the agitation and to ensure optimal patient management. Optimal level of sedation varies with the stimulation affecting the patient and is often achieved, for ventilated patients, at the deepest sedation, accompanied with sufficient analgesia.
Analgesia refers to the absence of pain or loss of sensitivity to pain without unconsciousness in response to stimulation that would normally be painful.
Noxious stimuli, such as pin-pricks or inflammation exceeding a certain threshold stimulus level in nociceptive nerve fibers (nociceptors), cause a nociception, i.e. a neuronal signal or perception that denotes the induced pain or injury. Nociception is transmitted in the Central Nervous System (CNS) via several different ascending pathways causing responses that can be cortical pain responses or subcortical stress responses. NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) effectively relief pain at a damaged tissue site, whereas opioids selectively affect the pain pathways in the region of the spinal cord or the brainstem. Local or regional anesthetic agents, for instance those used in epidural analgesia, block both the pain and the sensory pathways, for instance, in the spinal cord region.
Antinociception normally refers to the blocking or suppression of nociception in the pain pathways at the subcortical level. It may be described as subcortical analgesia, in distinction to preventing the perception of pain at the cortex.
The autonomic nervous system (ANS) is the ‘unconscious’ nervous system, which controls and regulates virtually all of our basic body functions, such as cardiac function, blood circulation and glandural secretion. The main parts of the ANS are the parasympathetical and sympathetical nervous branches. The sympathetical nervous system usually prepares us for high stress situations by speeding up the body functions. Under conditions of normal ANS regulation, the parasympathetical system restores the normal conditions in blood circulation by slowing down the heart rate. Pain, discomfort, and clinical stress may activate the sympathetical branch of the ANS and cause an increase in blood pressure, heart rate and adrenal secretions.
Electrocardiography (ECG) is a well-established method for assessing cardiac function by recording and analyzing the biopotential signals generated in the heart. Electrodes are attached on the skin of the chest with more peripheral references. The ECG is commonly used for diagnosing cardiac dysfunctions, various cardiac and circulatory diseases, and arrhythmias. Heart rate (HR), often derived from the ECG waveform, is one of the most important parameters characterizing the condition of a patient.
Respiration rate is another vital sign, which is often monitored even in basic patient care. In connection with anesthesia and sedation of ventilated patients, monitoring of the respiration is often combined with monitoring of gas exchange, which includes monitoring of inhaled and exhaled oxygen, carbon dioxide and anesthetic gases. In modern gas monitors, airway pressure (AWP) and gas flows are also measured in order to improve the safety and quality of the ventilation.
Blood pressure (maintaining blood circulation) is yet another vital sign obtained from a patient. It may be monitored either non-invasively (NIBP) or invasively (InvBP) using catheters inserted in the arteries or veins. The latter techniques are continuous and they allow a detailed monitoring of the regulation of the cardiac-circulatory and pulmonary functions.
Pulse oximetry is a well-established technique for measuring oxygen saturation (SpO2) in arterial blood. SpO2 is an important parameter, nowadays often called as the fourth vital sign, which relates to the adequacy of oxygen supply to peripheral tissues and organs. Pulse oximeters provide instantaneous in-vivo measurements of arterial oxygenation, and thereby an early warning of arterial hypoxemia, for example. Pulse oximeters also display a photoplethysmographic (PPG) pulse waveform, which can be related to tissue blood volume and blood flow, i.e. the blood circulation, at the site of the measurement, typically in finger or ear. The amplitude of a PPG waveform is a sensitive indicator of patient discomfort and pain, but it also reacts to non-noxious stimulations.
The photoplethysmographic signal obtained in a pulse oximeter also contains information of the respiratory function of the patient. U.S. Pat. No. 6,709,402 discloses a method for monitoring the respiration of a patient with a pulse oximeter. In this disclosure, a plethysmographic signal is processed to obtain a non-pulsatile DC signal component information, which is independent of the pulsation of the patient's heart. The DC signal component, and its increases and decreases over time, is used to determine the respiration frequency.
Another method for extracting the respiration rate from a plethysmographic signal is disclosed in U.S. Pat. No. 6,702,752. The method first extracts heart beat-to-beat interval information from the pulsatile AC component of the plethysmographic data. The variation of this heart rate data over time, an effect called Respiratory Sinus Arrhythmia (RSA), is then utilized to obtain the respiration rate of the patient.
In general anesthesia in machine-ventilated patients, the respiration rhythm of the patient is determined by the ventilator and the respiration rate is easily monitored by following the settings of the ventilator. In post anesthesia care units (PACUs), however, patients often breathe spontaneously. The analgesic drugs affect both the nociceptive status and the respiration function of the patient, since the said drugs may depress respiration. In finding an optimal balance between a sufficient pain relief and an undisturbed respiration, monitoring of both the respiration and the stress status of the patient would be important. Especially at an early period of the recovery, the patients are influenced by analgesic drugs given during the surgery and the effective concentrations of the analgesics may vary over time. Muscle relaxants administered to the patient during the surgery may also depress the respiration in post anesthesia care.
Analysis methods using the heart rate variability (HRV) are emerging techniques for diagnosing cardiac diseases, such as lack of oxygen supply to the cardiac muscle, and for characterizing the cardiac function and the condition of the patient in general. Fast changes in the heart rate are usually caused by the parasympathetical ANS control mediated in the vagal cranial nerve. Vagal control slows down the heart beat. The slow variations (<0.15 Hz) of the heart rate are mainly associated with sympathetical activity, which accelerates the heart beat. The ratio of the fast components of the HRV to the slow components of the HRV is often called the sympatho-vagal balance, which in emergency or during intense stress turns to sympathetical dominance.
The need for reliable monitoring of the adequacy of sedation is based on the quality of patient care and on economy related aspects. Balanced sedation reduces stress and there is firm evidence that adequate sedation decreases postoperative morbidity. Prolonged stress sensitizes the central pain pathways, which increases secretion of stress hormones. It may cause exposure to unwanted side effects during the recovery from the surgery. Too light sedation causes traumatic experiences both for the patient and for the anesthesia personnel. From economical point of view, too deep sedation may cause increased costs through extra use of drugs and time, and also extended time required for care. Too deep a sedation may also cause complications and prolong the usage time of expensive facilities, such as the intensive care theater.
EP Patent 0553162 proposes a method and apparatus for assessing the depth of anesthesia by using respiratory sinus arrhythmia (RSA) as a measure of the state of the brain. The document describes a method in which a parameter indicative of clustering of the heart beat pattern is determined from the ECG waveform relative to the beginning of each respiration cycle. This parameter is then compared with a reference value calculated using a test for randomness. The parameter is then compared with the reference value to derive a measurement of the depth of anesthesia. In particular with spontaneously breathing anesthetized patients, the clustering is proportional to the RSA, which decreases with deepening anesthesia. The heart rate changes influencing the clustering are primarily controlled by the parasympathetical branch of the ANS, and therefore, the depth of anesthesia is related to the parasympathetical activity. This, however, correlates poorly with sympathetical effects, i.e. with the pain and nociception, and therefore also poorly with the adequacy of analgesia. Furthermore, the clustering takes place differently in artificial over-pressure ventilation and in spontaneously breathing patients, as the heart rate always accelerates during the low pressure period of the respiration cycle and decelerates during the high pressure phase. The low pressure period occurs during the inspiration in case of spontaneously breathing patients and during the expiration in case of artificial ventilation. The proposed method works reasonably well for spontaneously breathing patients, who in addition have a large RSA, such as children, but often fails in connection with artificially ventilated older patients. Pain reduces RSA amplitudes, as does the deepening of anesthesia. As a result, a low value of clustering may suggest too deep an anesthesia, leading to a decrease in the level of hypnosis. This may, however, lead to a worse situation, as a result of which the patient may even wake up, especially if surgical stimulations are intense.
European Patent Application EP1273265 describes a simpler method for analyzing an RRI and a blood pressure (BP) time series. Furthermore, the method tries to make a clear distinction between the sympathetical and parasympathetical cardiovascular responses. The sympathetical responses correlating with the surgical stress increase the heart rate and blood pressure. The acceleration index of the heart rate and the index for the increase of the blood pressure are calculated using a filter, a kind of edge filter, which detects the increasing slopes in the values of RRI or BP, but neglects the decreasing values. The document suggests that these indices may be used as a measure of the adequacy of analgesia. However, the method lacks the specificity to noxious stimuli and detects also the variations caused by respiration and other increasing slopes resulting from normal sympathetical activation without noxious stimulation. For instance, when the patient is in light anesthesia, both the sympathetical and parasympathetical branch of the ANS is active and the indices show erroneously high values suggesting insufficient analgesia.
The above prior art technologies thus aim to describe the adequacy of anesthesia using a unidimensional concept for the depth of anesthesia. All prior art technologies that are claimed to measure the adequacy of analgesia show a considerable dependence on the level of hypnosis and, consequently, at light anesthesia without any noxious stimulations show a value that is usually associated with poor analgesia. A further drawback of the prior art technologies is that the measurement values show a considerable inter-patient variability. This makes their interpretation, i.e. the interpretation of the adequacy of anesthesia, difficult.
The prior art technologies also focus on recording the adequacy of anesthesia during the surgery and are not applicable post-operatively on spontaneously breathing patients.
International Patent Application WO 2004/034897 discloses a method and an apparatus for a plethysmographic based detection of nociception during anesthesia and sedation. In this method, predetermined pulse wave parameters are detected and compared with reference values obtained earlier by measuring the same parameters over a certain preceding time window. If a substantial change is detected in at least one pulse wave parameter, preferably in waveform amplitude, a change in another pulse wave parameter, preferably the position of the dicrotic notch, is determined. If both changes are substantial, the changes are displayed or recorded and interpreted as an indication of a nociceptive event. The method thus provides an indication of the presence of noxious stimulation. Since the method is based on detection of noxious events, i.e. short-lived changes in the signal, it cannot provide an indication of the basic level of antinociception.
U.S. Patent Application 2005/0010116 discloses a method and an apparatus for monitoring the condition of a patient under anesthesia or sedation. In this method, a mathematical index for probability of patient comfort is calculated. The probability index is obtained as a combination of physiological parameters extracted from a plethysmographic waveform, an ECG waveform, and/or electromyogram (EMG) power measured from patient forehead. Again, as in the above-referred WO application 2004/034897, the parameters in the probability index are referred to a certain reference value determined over a certain time window or at certain reference event. Since the index is only indicative of the probability of nociception, it cannot provide quantitative information of the level of nociception or of changes in the said level.
To sum up, automatic patient monitoring is important for accomplishing optimal pain relief in different phases of anesthesia or stressful treatment. However, prior art techniques are complicated as many parameters are required for the monitoring. The monitoring therefore requires measuring equipment, which is not always available in clinical set-ups.
The present invention seeks to eliminate the above drawbacks and to bring about a novel mechanism for determining the clinical stress of a patient by expanding the functionality of pulse oximeters, which are at present the standard of care for continuous monitoring of arterial oxygen saturation and therefore widely available in clinical set-ups.